Revised prognostic staging system for light chain amyloidosis incorporating cardiac biomarkers and serum free light chain measurements

Abstract

Purpose: Cardiac involvement predicts poor prognosis in light chain (AL) amyloidosis, and the current prognostic classification is based on cardiac biomarkers troponin-T (cTnT) and N-terminal pro-B-type natriuretic peptide (NT-ProBNP). However, long-term outcome is dependent on the underlying plasma cell clone, and incorporation of clonal characteristics may allow for better risk stratification.

Patients and methods: We developed a prognostic model based on 810 patients with newly diagnosed AL amyloidosis, which was further examined in two other datasets: 303 patients undergoing stem-cell transplantation, and 103 patients enrolled onto different clinical trials.

Results: We examined the prognostic value of plasma cell-related characteristics (ie, difference between involved and uninvolved light chain [FLC-diff], marrow plasma cell percentage, circulating plasma cells, plasma cell labeling index, and β(2) microglobulin). In a multivariate model that included these characteristics as well as cTnT and NT-ProBNP, only FLC-diff, cTnT, and NT-ProBNP were independently prognostic for overall survival (OS). Patients were assigned a score of 1 for each of FLC-diff ≥ 18 mg/dL, cTnT ≥ 0.025 ng/mL, and NT-ProBNP ≥ 1,800 pg/mL, creating stages I to IV with scores of 0 to 3 points, respectively. The proportions of patients with stages I, II, III and IV disease were 189 (25%), 206 (27%), 186 (25%) and 177 (23%), and their median OS from diagnosis was 94.1, 40.3, 14, and 5.8 months, respectively (P < .001). This classification system was validated in the other datasets.

Conclusion: Incorporation of serum FLC-diff into the current staging system improves risk stratification for patients with AL amyloidosis and will help develop risk-adapted therapies for AL amyloidosis.

Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.

(A) Kaplan-Meier curves for overall survival (OS) from diagnosis among 758 patients based on the new staging system; shaded areas indicate the 95% CI estimates. (B) Kaplan-Meier curves for OS from diagnosis among 512 patients based on the staging system, substituting B-type natriuretic peptide for N-terminal pro–B-type natriuretic peptide. (A, B) Patients surviving beyond 5 years were censored at the 5-year mark. Numbers of patients at risk at each time point are shown below the x-axis. Survival curves were compared using log-rank test.

Fig 2.

(A) Kaplan-Meier curves for overall survival (OS) from diagnosis among the subgroup of 583 patients based on the new staging system. Patients surviving beyond 5 years were censored at the 5-year mark. (B) Kaplan-Meier curves for OS from stem-cell transplantation among 303 patients based on the new staging system. Patients surviving beyond 4 years were censored at the 4-year mark. (C) Kaplan-Meier curves for OS from time of trial entry among 103 patients enrolled onto different trials based on the new staging system. Patients surviving beyond 4 years were censored at the 4-year mark. (A, B, C) Numbers of patients at risk at each time point are shown below the x-axis. Survival curves were compared using log-rank test.